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CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis

Abstract

Purpose

This study aimed at investigating the function and significance of CD110 expression in pancreatic cancer.

Methods

We performed immunohistochemical staining for CD110 expression in tumor samples from 86 patients with pancreatic cancer. We evaluated clinical outcomes and other clinicopathological factors to determine the significance of CD110 on survival and liver metastasis. We examine thrombopoietin–CD110 signaling in cancer cell extravasation in vitro and in vivo. We investigated the effects of CD110 knockdown on liver metastasis in a splenic xenograft mouse model.

Results

CD110 expression in cancer cells was associated with low-histological-grade invasive ductal carcinoma, and patients with high CD110 expression had poorer prognosis (P = 0.0003). High CD110 expression was an independent predictor of liver metastasis (P = 0.0422). Knockdown of CD110 expression significantly attenuated cell migration and invasion. Treatment with thrombopoietin promoted pancreatic cancer cell extravasation. In the presence of thrombopoietin, CD110 increased cell viability through the activation of the ERK–MYC signaling pathway. Knockdown of CD110 expression inhibited liver metastases in the mouse model.

Conclusions

CD110 promotes pancreatic cancer progression and it may serve as a predictive factor for liver metastasis.

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Acknowledgements

We are grateful to Emiko Manabe and Shoko Sadatomi (Department of Surgery and Oncology, Kyushu University) for skillful technical assistance. Zilong Yan is the recipient of Rotary Yoneyama Memorial Foundation scholarship [http://www.rotary-yoneyama.or.jp]. We thank Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript. This work was supported by JSPS KAKENHI (Grant number: 26108010, 26293305, 15K10185, 25713050, 16K15621, 16K10601, 16K10600, 16H05417, 15K15498, 15H04933, 16H05418, 17H04284, 17K19602 and 17K19605).

Author information

Correspondence to Kenoki Ohuchida.

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All the authors declare that there is no conflict of interest in this work.

Ethical approval

This study was approved by the Kyushu University Institutional Review Board (Fukuoka, Japan).

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Informed consent was obtained from all individual participants included in the study.

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Yan, Z., Ohuchida, K., Zheng, B. et al. CD110 promotes pancreatic cancer progression and its expression is correlated with poor prognosis. J Cancer Res Clin Oncol 145, 1147–1164 (2019). https://doi.org/10.1007/s00432-019-02860-z

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Keywords

  • Pancreatic cancer
  • CD110
  • TPO
  • Liver metastasis
  • Transendothelial migration